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<div about="/news-events/news-releases/international-study-reveals-new-genetic-clues-age-related-macular-degeneration" typeof="sioc:Item foaf:Document" class="ds-1col node node--nih-news-release news-release featured-media-floated view-mode-full node--full node--nih-news-release--full clearfix">
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<p class="publishdate"><span class="tag-term">News Release</span></p><p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2015-12-21T11:00:00-05:00" class="date-display-single">Monday, December 21, 2015</span></p><h1>International study reveals new genetic clues to age-related macular degeneration</h1><p class="subtitle">
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NIH-funded research provides framework for future studies of AMD biology, therapy. </p><div class="featured-media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
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<picture title="An info graphic with AMD statistics">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large-extra/public/news-events/news-releases/2015/20151221-macular-degeneration.jpg?itok=Ef1bZf0C&timestamp=1450710727 1x" media="screen and (min-width: 1100px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large/public/news-events/news-releases/2015/20151221-macular-degeneration.jpg?itok=ciBn1eLg&timestamp=1450710727 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/news-events/news-releases/2015/20151221-macular-degeneration.jpg?itok=skcROWcJ&timestamp=1450710727 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium-small/public/news-events/news-releases/2015/20151221-macular-degeneration.jpg?itok=HtLMGO8Y&timestamp=1450710727 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-small/public/news-events/news-releases/2015/20151221-macular-degeneration.jpg?itok=oKxmPAJM&timestamp=1450710727 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media__breakpoint-tiny_/public/news-events/news-releases/2015/20151221-macular-degeneration.jpg?itok=YoUS4bkp&timestamp=1450710727 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/news-events/news-releases/2015/20151221-macular-degeneration.jpg?itok=skcROWcJ&timestamp=1450710727" alt="An info graphic with AMD statistics" title="An info graphic with AMD statistics" />
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</picture><span class="caption">Between 2010 and 2050, the estimated number of people with AMD will more than double from 2.1 million to 5.4 million.</span></div>
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</div><p>An international study of about 43,000 people has significantly expanded the number of genetic factors known to play a role in age-related macular degeneration (AMD), a leading cause of vision loss among people age 50 and older. Supported by the National Eye Institute (NEI), part of the National Institutes of Health, the findings may help improve our understanding of the biological processes that lead to AMD and identify new therapeutic targets for potential drug development. </p>
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<p>AMD is a progressive disease that causes the death of the retinal photoreceptors, the light-sensitive cells at the back of the eye. The most severe damage occurs in the macula, a small area of the retina that is needed for sharp, central vision necessary for reading, driving and other daily tasks. There are currently no Food and Drug Administration-approved treatments for the more common form of advanced AMD, called geographic atrophy or “dry” AMD. While therapies for the other advanced form, neovascular or “wet” AMD, can successfully halt the growth of abnormal, leaky blood vessels in the eye, the therapies do not cure the condition, nor do they work for everyone.</p>
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<p>AMD is caused by a combination of genetic, environmental and lifestyle risk factors. For example, smoking increases the risk of AMD, while eating leafy greens and fish, such as salmon, halibut, and tuna, may reduce the risk. Up to this point, researchers had identified 21 regions of the genome—called loci—that influence the risk of AMD. The new research, published in <em>Nature Genetics</em>, brings the number up to 34 loci.</p>
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||
<p>The International AMD Genomics Consortium, which includes 26 centers worldwide, collected and analyzed the genetic data from 43,566 people of predominantly European ancestry to systematically identify common and rare variations in genetic coding — called variants — associated with AMD. Common variants generally have an indirect association with a disease. Rare variants, by contrast, are more likely to alter protein expression or function and therefore have a direct or causal association with a disease. Rare variants were defined as those found in less than 1 percent of the study population.</p>
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||
<p>The study included about 23,000 participants with AMD and 20,000 without it. The researchers analyzed DNA samples from both groups, surveying most of the genome, but also focusing in on distinct loci already known or suspected to be associated with AMD. Next, they compared the participants’ DNA to a reference dataset called the 1000 Genomes project, yielding more than 12 million genetic variants of potential interest. Finally, they went back to the participants’ DNA samples, looking at all 12 million variants, to see if any were found more or less often in people with AMD than those without it.</p>
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<p>“The investigation is akin to looking at a Google map of the United States and attempting to pinpoint several leaders and satellite operations in a crime syndicate,” said a co-leader of the study, Anand Swaroop, Ph.D., chief of NEI’s Neurobiology-Neurodegeneration and Repair Laboratory. “It’s possible to find the key players by zooming in and seeing specific regions in rich detail, but first you have to know where to look. Pooling the genetic information from such a large population is what allowed us to look across the genome for possible culprits in AMD, even very small, very rare ones.”</p>
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||
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<p>The researchers have now discovered a total of 52 genetic variants that are associated with AMD. These variants are located among 34 loci, 16 of which had not been previously associated with AMD.</p>
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<p>“If you think of these loci as points on our Google map in our search for the crime syndicate members, or the genetic causes of AMD, in some cases they are as big as a zip code, but in other cases they pinpoint an area as narrowly defined as a few houses within a neighborhood subdivision,” Dr. Swaroop said.</p>
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<p>“These variants provide a foundation for genetic studies of AMD going forward,” said one of the senior authors, Jonathan L. Haines, Ph.D., of Case Western Reserve University in Cleveland. “The next step is to investigate what the variants are doing to the genes and how they affect gene function. Do they turn them on or off? Do they interact with other genes spurring a series of events along a pathway that leads to AMD?” </p>
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<p>The study findings also bolster associations between AMD and two genes, CFH and TIMP3, which had each previously been linked to AMD. CFH was the very first disease-linked gene to be found through a genome-wide association study. TIMP3 had earlier been linked to Sorsby’s fundus dystrophy, a rare disease that is similar to AMD clinically, but that tends to affect people before the age of 45.</p>
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<p>For the first time the researchers also identified a variant specific to the neovascular form of AMD, which may point to reasons why therapy for this form of AMD is effective for some people but not everyone.</p>
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<p>Additionally, 10 of the variants point to genes involved in maintaining the extracellular matrix, the nonliving material amongst cells that provides structural support and nutrients. Researchers have theorized that abnormalities of the extracellular matrix occur in people with a subtype of AMD that develops without early-stage signs, or that quickly worsens before such signs are detected. If confirmed, a connection between AMD and these extracellular matrix genes may allow for predictive genetic tests and more effective therapies for people with this type of AMD.</p>
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<p>“Even with the pooling of genetic information from such a large population, the variants identified by the international consortium still cannot account for all of the heritability of AMD,” said Grace L. Shen, Ph.D., a group leader and director of the retinal diseases program at NEI. “We are, however, on track for discovering important variant genes that may play a role in AMD heritability.”</p>
|
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<p>The study was funded in part by NEI Intramural Research Program and by NEI grants: EY023164, EY012118, EY022310, EY0022005, EY016862, EY09859, EY06594, EY021532, EY0105712, EY021900, EY017362, EY13824, EY009611, EY014428, EY018660 and EY013435. The study also was supported by NIH grants from the National Human Genome Research Institute (HG006513, HG007022, 1U01HG006389), the National Institute on Aging (AG019085), and the National Center for Advancing Translational Sciences (UL1TR000427). For more information, see the study’s acknowledgements section.</p>
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<p><strong>About the National Institutes of Health (NIH):</strong>
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NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <a href="/">www.nih.gov</a>.</p>
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<h3>Reference </h3>The International AMD Genomics Consortium, “Insights into Rare and Common Genetic Variation from a Large Study of Age-Related Macular Degeneration,” Nature Genetics, online December 21, 2015. DOI:10.1038/ng.3448</div>
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